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CAR T-cell Therapy

PBCAR0191 for Blood Cancer

Phase 1
Recruiting
Research Sponsored by Imugene Limited
Eligibility Criteria Checklist
Specific guidelines that determine who can or cannot participate in a clinical trial
Must have
Subject has adequate bone marrow, renal, hepatic, pulmonary, and cardiac function defined as: Estimated glomerular filtration rate (eGFR) >30 mL/min/1.73 m2 (calculated using the CKD-EPI equation [Levey et al, 2009]). If there is a concern that eGFR calculation is not an accurate reflection of renal function, a 24-hour urine collection for creatinine clearance may be used at the investigator's discretion. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels both ≤3 times of upper limit of normal (ULN), unless there is suspected disease in the liver. Total bilirubin <2.0 mg/dL, except in subjects with Gilbert's syndrome. Platelet count ≥50,000/μL and absolute neutrophil count of ≥1000/ μL. Platelet transfusions within 14 days of screening are not allowed except for subjects in B-ALL disease cohort with extensive bone marrow disease burden, in which case adequate bone marrow recovery after prior treatment is required to be documented. C-reactive protein (CRP) <2x ULN; subjects with CRP elevation within 2x ULN, ruling out infectious cause will be required. Left ventricular ejection fraction >45% as assessed by echocardiogram (ECHO) or multiple gated acquisition scan performed within 1 month before starting lymphodepleting chemotherapy. ECHO results performed within 6 months before Screening and at least 28 days after the last cancer treatment may be acceptable if the subject has not received any treatment with cardiotoxicity risks. No clinically significant evidence of pericardial effusion or pleural effusion causing clinical symptoms and needing immediate intervention, based on the investigator's opinion. Any known effusion must be stable without need for drainage within 2 weeks of enrollment. No clinically significant renal/pulmonary comorbidities. Baseline oxygen saturation >92% on room air.
Subject has unequivocal r/r CD19+ B-ALL that has been confirmed by morphology, flow cytometry, or a validated minimal residual disease assay.
Must not have
Requirement for urgent therapy due to tumor mass effects such as bowel obstruction or blood vessel compression.
No active central nervous system (CNS) disease. Subjects with a history of CNS involvement must have a documented CR on at least 2 imaging studies at least 3 months apart (with no masses in parenchyma and no ocular involvement) and a negative cerebrospinal fluid cytology on at least 2 evaluations (one evaluation may be during the Screening Period and the other must be at least 3 months prior).
Timeline
Screening 3 weeks
Treatment Varies
Follow Up up to day 720
Awards & highlights
No Placebo-Only Group

Summary

This trial tests a new therapy using specially altered immune cells in adults with certain types of blood cancers that have not responded to other treatments. The goal is to find a safe and effective amount.

Who is the study for?
Adults with aggressive CD19+ B-cell Non-Hodgkin's Lymphoma (NHL) or relapsed/refractory B-cell Acute Lymphoblastic Leukemia (ALL), who have tried at least two prior treatments, can join this trial. They should not have severe heart, lung, kidney, liver issues or active infections and must be HIV negative. Those with a history of CNS disease need to show clear recovery.
What is being tested?
The study is testing PBCAR0191 in combination with Fludarabine and Cyclophosphamide for safety and effectiveness in treating NHL and ALL. It involves gradually increasing the dose to find the best balance between benefits and side effects.
What are the potential side effects?
Potential side effects may include reactions related to immune system activation such as fever, fatigue, nausea; blood cell count changes leading to increased infection risk; organ inflammation; plus specific risks from chemotherapy like hair loss and mouth sores.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below
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My leukemia (B-ALL) is resistant or has returned and tests confirm it targets CD19.
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I've had no more than 2 treatments after my CAR T-cell therapy.
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I had CAR T therapy for cancer, responded well initially, but then my cancer came back.
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My aggressive B-cell NHL is confirmed to be CD19 positive from my last relapse.
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I do not have serious kidney or lung conditions.
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My disease can be measured or seen on scans.
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I am fully active or restricted in physically strenuous activity but can do light work.
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I have had 7 or fewer treatments for my cancer.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:
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I need urgent treatment because my tumor is causing blockages or pressing on blood vessels.
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I do not have active brain or spinal cord disease, and tests confirm this.
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I have a condition that significantly weakens my immune system.
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I do not have serious heart rhythm problems.
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I have a history of blood clots or significant bleeding disorders.
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I have a genetic condition like Fanconi anemia affecting my bone marrow.
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I do not have an active autoimmune disease needing strong medication now.
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I have an active condition where my red blood cells are being destroyed faster than they can be made.
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My leukemia is either Burkitt (L3 ALL) or mixed-lineage.
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I have never had, nor do I currently have, any brain or spinal cord diseases.
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I am experiencing symptoms of graft-versus-host disease.

Timeline

Screening ~ 3 weeks
Treatment ~ Varies
Follow Up ~up to day 720
This trial's timeline: 3 weeks for screening, Varies for treatment, and up to day 720 for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.
Primary study objectives
Phase 1b Dose Expansion: Objective response rate (ORR): Dose expansion only
Secondary study objectives
Complete response (CR) rate
Duration of Response (DoR)
Number of Participants with AEs
+4 more

Awards & Highlights

No Placebo-Only Group
All patients enrolled in this study will receive some form of active treatment.

Trial Design

6Treatment groups
Experimental Treatment
Group I: Dose level 4cExperimental Treatment3 Interventions
Azer-cel, 1000 x 10\^6 CAR T cells (flat dose) given as 2 administrations of 500 × 106 cells/per dose on Day 0 and Day 5.
Group II: Dose Level 4bExperimental Treatment5 Interventions
Azer-cel, 500 x 10\^6 CAR T cells (flat dose)
Group III: Dose Level 4Experimental Treatment3 Interventions
Azer-cel, 6 x 10\^6 CAR T cells per kg body weight as 2 administrations of 3 x 10\^6 CAR T cells per kg body weight administered after a single lymphodepletion.
Group IV: Dose Level 3aExperimental Treatment3 Interventions
Azer-cel, 3 x 10\^6 CAR T cells per kg body weight.
Group V: Dose Level 2Experimental Treatment3 Interventions
Azer-cel, 1 x 10\^6 CAR T cells per kg body weight
Group VI: Dose Level 1Experimental Treatment3 Interventions
Azer-cel 3 x 10\^5 CAR T cells per kilogram (kg) body weight. Route of Administration: Intravenous infusion.
Treatment
First Studied
Drug Approval Stage
How many patients have taken this drug
IL-2
2007
Completed Phase 4
~1100
Bendamustine
2015
Completed Phase 3
~3230
Fludarabine
2012
Completed Phase 4
~1860
Cyclophosphamide
2010
Completed Phase 4
~2310

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.
Mechanism Of Action
Side Effect Profile
Prior Approvals
Other Research
Non-Hodgkin's Lymphoma (NHL) treatments include chemotherapy, monoclonal antibodies, and Chimeric Antigen Receptor (CAR) T-cell therapy. CAR T-cell therapy, such as PBCAR0191, involves modifying a patient's T-cells to express a receptor specific to the CD19 antigen found on B-cells. These engineered T-cells are then infused back into the patient, where they seek out and destroy CD19-positive cancer cells. This targeted approach is significant for NHL patients as it offers a personalized treatment option that can lead to durable remissions, especially in relapsed or refractory cases where traditional therapies may have failed.

Find a Location

Who is running the clinical trial?

Imugene LimitedLead Sponsor
6 Previous Clinical Trials
209 Total Patients Enrolled
Precision BioSciences, Inc.Lead Sponsor
5 Previous Clinical Trials
199 Total Patients Enrolled
Monika Vainorius, MDStudy ChairPrecision BioSciences, Inc.
6 Previous Clinical Trials
423 Total Patients Enrolled
John Byon, MD, PhDStudy ChairImugene Limited
1 Previous Clinical Trials
31 Total Patients Enrolled

Media Library

PBCAR0191 (CAR T-cell Therapy) Clinical Trial Eligibility Overview. Trial Name: NCT03666000 — Phase 1
Acute Lymphoblastic Leukemia Research Study Groups: Dose level 4c, Dose Level 1, Dose Level 2, Dose Level 3a, Dose Level 4, Dose Level 4b
Acute Lymphoblastic Leukemia Clinical Trial 2023: PBCAR0191 Highlights & Side Effects. Trial Name: NCT03666000 — Phase 1
PBCAR0191 (CAR T-cell Therapy) 2023 Treatment Timeline for Medical Study. Trial Name: NCT03666000 — Phase 1
~9 spots leftby Jun 2025